-
American heart journal · Jun 2018
Randomized Controlled Trial Multicenter StudyThe design and rationale for the Dapagliflozin Effect on Cardiovascular Events (DECLARE)-TIMI 58 Trial.
- Stephen D Wiviott, Itamar Raz, Marc P Bonaca, Ofri Mosenzon, Eri T Kato, Avivit Cahn, Michael G Silverman, Sameer Bansilal, Deepak L Bhatt, Lawrence A Leiter, Darren K McGuire, John Ph Wilding, Ingrid Am Gause-Nilsson, Anna Maria Langkilde, Peter A Johansson, and Marc S Sabatine.
- TIMI Study Group, Cardiovascular Division, Brigham and Women's Hospital, Boston, MA. Electronic address: swiviott@partners.org.
- Am. Heart J. 2018 Jun 1; 200: 83-89.
BackgroundDapagliflozin is a sodium-glucose co-transporter-2 (SGLT-2) inhibitor that reduces blood glucose in patients with type 2 diabetes mellitus (T2DM) by promoting glycosuria via inhibiting urinary glucose reabsorption. In addition to improving blood glucose control, treatment with dapagliflozin results in glucose-induced osmotic diuresis, weight loss, and blood pressure lowering. Previous trials of SGLT-2 inhibitors showed reductions in cardiovascular (CV) events, including CV death and hospitalization for heart failure, and ischemic events in patients with atherosclerotic cardiovascular disease (ASCVD).Research Design And MethodsDECLARE-TIMI 58 (NCT01730534) is a phase 3b randomized, double-blind, placebo-controlled trial designed to evaluate the CV safety and efficacy of dapagliflozin that has completed randomization of 17,160 patients with T2DM and a history of either established ASCVD (n=6,971) or multiple risk factors for ASCVD (n=10,189). Patients were randomized in a 1:1 fashion to dapagliflozin 10 mg or matching placebo. The primary safety outcome is the time to the first event of the composite of CV death, myocardial infarction, or ischemic stroke (major adverse cardiovascular events; MACEs). The co-primary efficacy outcomes are the composite of CV death, myocardial infarction, or ischemic stroke and the composite of CV death or hospitalization for heart failure. This event-driven trial will continue until at least 1,390 subjects have a MACE outcome, thereby providing >99% power to test for the primary outcome of safety of dapagliflozin measured by rejecting the hypothesis that the upper bound of the CI >1.3 for the primary outcome of MACE, as well as 85% power to detect a 15% relative risk reduction in MACE and an estimated 87% power to detect a 20% reduction in the composite of CV death or hospitalization for heart failure at a 1-sided α level of .0231.ConclusionThe DECLARE-TIMI 58 trial is testing the hypotheses that dapagliflozin is safe (does not increase) and may reduce the occurrence of major CV events. DECLARE-TIMI 58 is the largest study to address this question with an SGLT-2 inhibitor in patients with T2DM and with established CV disease and without CV disease but with multiple risk factors.Copyright © 2018 Elsevier Inc. All rights reserved.
Notes
Knowledge, pearl, summary or comment to share?You can also include formatting, links, images and footnotes in your notes
- Simple formatting can be added to notes, such as
*italics*
,_underline_
or**bold**
. - Superscript can be denoted by
<sup>text</sup>
and subscript<sub>text</sub>
. - Numbered or bulleted lists can be created using either numbered lines
1. 2. 3.
, hyphens-
or asterisks*
. - Links can be included with:
[my link to pubmed](http://pubmed.com)
- Images can be included with:
![alt text](https://bestmedicaljournal.com/study_graph.jpg "Image Title Text")
- For footnotes use
[^1](This is a footnote.)
inline. - Or use an inline reference
[^1]
to refer to a longer footnote elseweher in the document[^1]: This is a long footnote.
.